title: Imaging bone morphogenetic protein 7 induced cell cycle arrest in experimental gliomas.
abstract: Bone morphogenetic protein 7 (BMP-7) belongs to the superfamily of transforming growth factor β-like cytokines, which can act either as tumor suppressors or as tumor promoters depending on cell type and differentiation. Our investigations focused on analyzing the effects of BMP-7 during glioma cell proliferation in vitro and in vivo. BMP-7 treatment decreased the proliferation of Gli36ΔEGFR-LITG glioma cells up to 50%through a cell cycle arrest in the G(1) phase but not by induction of apoptosis. This effect was mediated by the modulation of the expression and phosphorylation of cyclin-dependent kinase 2, cyclin-dependent kinase inhibitor p21, and downstream retinoblastoma protein. Furthermore, in vivo optical imaging of luciferase activity of Gli36ΔEGFR-LITG cells implanted intracranially into nude mice in the presence or absence of BMP-7 treatment corroborated the antiproliferative effects of this cytokine. This report clearly underlines the tumor-suppressive role of BMP-7 in glioma-derived cells. Taken together, our results indicate that manipulating the BMP/transforming growth factor β signaling cascade may serve as a new strategy for imaging-guided molecular-targeted therapy of malignant gliomas.
authors.affiliation: European Institute for Molecular Imaging, University of Münster, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Klose
authors.forename: Yannic
authors.initials: Y
authors.lastname: Waerzeggers
authors.forename: Parisa
authors.initials: P
authors.lastname: Monfared
authors.forename: Slobodan
authors.initials: S
authors.lastname: Vukicevic
authors.forename: Eric L
authors.initials: EL
authors.lastname: Kaijzel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Winkeler
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D016193:G1 Phase; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D049449:Luminescence; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D055419:Bone Morphogenetic Protein 7; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D008156:Luciferases; D051357:Cyclin-Dependent Kinase 2